The integrity of thalamo-dorsolateral prefrontal cortex tract: a key factor in residual consciousness in disorders of consciousness patients.

Background: The mesocircuit model describes a complex network that includes the prefrontal cortical-striatopallidal-thalamo-cortical loop systems and is involved in the mechanism underlying consciousness in patients with disorders of consciousness (DoC). Inhibitory signals to the thalamus become hyperactive in DoC patients, leading to a loss of consciousness. Reactivating this mesocircuit system is important for recovering consciousness in these patients. We investigated how the residual integrity of the thalamo-dorsolateral prefrontal cortex tract (TDLPFCT) influences consciousness in patients with DoC. Methods: This retrospective case-control study included three groups: prolonged DoC (n = 20), stroke without DoC (n = 20), and healthy controls (n = 20). Diffusion tensor imaging (DTI) was performed at least 4 weeks after the onset. Thalamo-DLPFC tracts were reconstructed using diffusion tensor tractography, and fractional anisotropy (FA) and tract volume (TV) were measured for each hemisphere. Consciousness was assessed using the revised coma recovery scale (CRS-R) within a week of brain imaging. Results: Significant differences in DLPFCT TV were observed across all three groups, in both affected and less-affected lobes, with the DoC group showing the greatest reduction. A significant correlation was found between the TV of the less-affected TDLPFCT and CRS-R score. Conclusion: The integrity of the TDLPFCT, particularly in the less affected hemisphere, is associated with consciousness levels in patients with prolonged DoC. This finding suggests its potential importance in assessing prognosis and further developing therapeutic strategies for patients with DoC.

Investigating the link between antipsychotic use and post-stroke infections in older people: multi-centre propensity score analysis.

BACKGROUND: The risk of stroke increases with age, and although previous reports have suggested that infection risk may increase with antipsychotic use, relevant studies after stroke are scarce. We aimed to investigate whether antipsychotics increase post-stroke infection risk in the acute stroke period. METHODS: This propensity score matching study included adults diagnosed with first-ever stroke between 2011 and 2020 at five university hospitals. In-hospital antipsychotic exposure was defined as any administration during hospitalisation for stroke. The primary outcome was post-stroke infection after the first 2 days of hospitalisation, and the secondary outcome was the presence of pneumonia, bacteraemia and/or bacteriuria. RESULT: Among 23,885 first-ever stroke patients, 2,773 antipsychotic users (age 71.6 ± 12.4, male 54.6%) and 2,773 non-users (age 71.2 ± 13.2, male 54.6%) were selected as matched cohorts. After adjusting for propensity score, antipsychotics were not associated with an increased risk of post-stroke infection (odds ratio 0.99, 95% confidence interval 0.87-1.14). CONCLUSION: While our study did not find conclusive evidence linking antipsychotic medication to an increased risk of post-stroke infection, prescribing these medications should still be approached with prudence. Until further research can provide more definitive insights, clinicians should carefully weigh the potential infection risks when considering antipsychotic treatment during the acute stroke care period.

Optimized trans-cranial direct current stimulation for prolonged consciousness disorder in a patient with titanium mesh cranioplasty.

BACKGROUND: Transcranial direct current stimulation (tDCS) has been used for the restoration of awareness in patients with a minimal consciousness state (MCS). Most brains of patients in MCS may structurally and electrophysiologically differ from un-damaged brains. Moreover, tDCS is currently contraindicated for patients with craniotomy or skull with metallic implants. CASE PRESENTATION: We present a case with prolonged MCS over 1 year, who had severe brain damage, ventriculoperitoneal shunt, and cranioplasty with a titanium mesh, which was treated with tDCS which optimized with the simulation of the electric field based on the patient's brain MRI. The patient was resulting in emergence from MCS. Six months later, she ate meals orally and started walking with assistance. DISCUSSION AND PERSPECTIVE: This personalized simulation based on MRI would make the treatment available even to patients with severe brain structural changes and metallic instrumentation.

Phase Angle as a Marker of Physical Function in Non-Sarcopenic Rheumatoid Arthritis.

Background: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease. Most patients with RA face a barrier to participation in social activities or exercise due to joint pain, despite the beneficial effects of exercise and physical activity. Thus, RA may be a risk factor for sarcopenia in the clinical field. Bioelectrical impedance analysis-derived phase angle (PhA) reflects cellular health and is correlated with the prognosis of various diseases. However, its association with physical function in non-sarcopenic RA female patients remains unclear. We evaluated the association between PhA values and various physical function measures in female patients with non-sarcopenic RA. Methods: Thirty-five participants with RA were screened. One met the criteria for sarcopenia. Finally, 34 patients with non-sarcopenic RA were enrolled. This cross-sectional retrospective study evaluated upper- and lower-extremity strengths, cross-sectional area of rectus femoris, 6 min walking test, Borg scale score, sit-to-stand test, and physical function and mental health from 36-Item Short Form Health Survey scores. Results: In total, 34 female participants (mean age = 49.74 ± 8.15 years) were enrolled. In non-sarcopenic RA patients, PhA was significantly correlated with BMI and ASM/(height)2. Multicollinearity was not detected among the independent variables (VIF < 5). The final multivariable regression model identified ASM/height2 as a significant predictor of PhA among non-sarcopenic RA patients. Conclusion: Multivariable linear regression analyses identified appendicular skeletal muscle mass as a significant predictor of PhA. Bioelectrical impedance analysis-derived PhA is a valuable guidance tool for RA management. PhA can be a useful clinical biomarker of muscle status in non-sarcopenic RA patients.

An Exercise Prescription for Patients with Stroke and Sarcopenia Based on the Modified Delphi Study.

BACKGROUND: We aimed to develop a consensus on the need for and priorities of exercise to treat preexisting sarcopenia with hemiplegic stroke. METHODS: A modified three-round Delphi study was conducted. The panelists responded to the questionnaire on a 7-point Likert scale. Responses were returned with descriptive statistics in the next round. Consensus was defined as >75% agreement (score of 5-7) with a median > 5. The percentage of strong agreement (score of 6-7) and Kendall's coefficient of concordance were calculated to demonstrate a more refined interpretation of the consensus. RESULTS: Fifteen panelists contributed to all rounds. The need for exercise was demonstrated. The consensus was reached on 53 of 58 items in the first round and all items in the second and final rounds. The percentage of strong agreement was high for all but eight items. CONCLUSIONS: This study is the first Delphi study to investigate the need for and priorities of exercise for treating preexisting sarcopenia in stroke hemiplegia. We present a standard recommendation including 57 priorities and a strong recommendation including 49 priorities. The eight items that were excluded reflected factors that are less important to hemiplegic patients with poor balance, cognitive decline, or mental vulnerability.

Electric field simulation and appropriate electrode positioning for optimized transcranial direct current stimulation of stroke patients: an in Silico model.

Transcranial Direct Current Stimulation (tDCS) has benefits for motor rehabilitation in stroke patients, but its clinical application is limited due to inter-individual heterogeneous effects. Recently, optimized tDCS that considers individual brain structure has been proposed, but the utility thereof has not been studied in detail. We explored whether optimized tDCS provides unique electrode positions for each patient and creates a higher target electric field than the conventional approach. A comparative within-subject simulation study was conducted using data collected for a randomized controlled study evaluating the effect of optimized tDCS on upper extremity function in stroke patients. Using Neurophet tES LAB 3.0 software, individual brain models were created based on magnetic resonance images and tDCS simulations were performed for each of the conventional and optimized configurations. A comparison of electrode positions between conventional tDCS and optimized tDCS was quantified by calculation of Euclidean distances. A total of 21 stroke patients were studied. Optimized tDCS produced a higher electric field in the hand motor region than conventional tDCS, with an average improvement of 20% and a maximum of 52%. The electrode montage for optimized tDCS was unique to each patient and exhibited various configurations that differed from electrode placement of conventional tDCS. Optimized tDCS afforded a higher electric field in the target of a stroke patient compared to conventional tDCS, which was made possible by appropriately positioning the electrodes. Our findings may encourage further trials on optimized tDCS for motor rehabilitation after stroke.

Prediction of In-Hospital Mortality for Ischemic Cardiogenic Shock Requiring Venoarterial Extracorporeal Membrane Oxygenation.

BACKGROUND: Clinical outcome of ischemic cardiogenic shock (CS) requiring extracorporeal membrane oxygenation is highly variable, necessitating appropriate assessment of prognosis. However, a systemic predictive model estimating the mortality of refractory ischemic CS is lacking. The PRECISE (Prediction of In-Hospital Mortality for Patients With Refractory Ischemic Cardiogenic Shock Requiring Veno-Arterial Extracorporeal Membrane Oxygenation Support) score was developed to predict the prognosis of refractory ischemic CS due to acute myocardial infarction. METHODS AND RESULTS: Data were obtained from the multicenter CS registry RESCUE (Retrospective and Prospective Observational Study to Investigate Clinical Outcomes and Efficacy of Left Ventricular Assist Device for Korean Patients With Cardiogenic Shock) that consists of 322 patients with acute myocardial infarction complicated by refractory ischemic CS requiring extracorporeal membrane oxygenation support. Fifteen parameters were selected to assess in-hospital mortality. The developed model was validated internally and externally using an independent external cohort (n=138). Among 322 patients, 138 (42.9%) survived postdischarge. Fifteen predictors were included for model development: age, diastolic blood pressure, hypertension, chronic kidney disease, peak lactic acid, serum creatinine, lowest left ventricular ejection fraction, vasoactive inotropic score, shock to extracorporeal membrane oxygenation insertion time, extracorporeal cardiopulmonary resuscitation, use of intra-aortic balloon pump, continuous renal replacement therapy, mechanical ventilator, successful coronary revascularization, and staged percutaneous coronary intervention. The PRECISE score yielded a high area under the receiver-operating characteristic curve (0.894 [95% CI, 0.860-0.927]). External validation and calibration resulted in competent sensitivity (area under the receiver-operating characteristic curve, 0.895 [95% CI, 0.853-0.930]). CONCLUSIONS: The PRECISE score demonstrated high predictive performance and directly translates into the expected in-hospital mortality rate. The PRECISE score may be used to support clinical decision-making in ischemic CS (www.theprecisescore.com). REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02985008.

Associations of combined polygenic risk score and glycemic status with atrial fibrillation, coronary artery disease and ischemic stroke.

BACKGROUND: It is unknown whether high hemoglobin A1c (HbA1c) is associated with increases in the risk of cardiovascular disease among individuals with elevated genetic susceptibility. We aimed to investigate the association between HbA1c and atrial fibrillation (AF), coronary artery disease (CAD), and ischemic stroke according to the polygenic risk score (PRS). METHODS: The UK Biobank cohort included 502,442 participants aged 40-70 years who were recruited from 22 assessment centers across the United Kingdom from 2006 to 2010. This study included 305,605 unrelated individuals with available PRS and assessed new-onset AF, CAD, and ischemic stroke. The participants were divided into tertiles based on the validated PRS for each outcome. Within each PRS tertiles, the risks of incident events associated with HbA1c levels were investigated and compared with HbA1c < 5.7% and low PRS. Data were analyzed from November 2022 to May 2023. RESULTS: Of 305,605 individuals, 161,605 (52.9%) were female, and the mean (SD) age was 56.6 (8.1) years. During a median follow-up of 11.9 (interquartile range 11.1-12.6) years, the incidences of AF, CAD, and ischemic stroke were 4.6, 2.9 and 1.1 per 100 person-years, respectively. Compared to individuals with HbA1c < 5.7% and low PRS, individuals with HbA1c ≥ 6.5% and high PRS had a 2.67-times higher risk for AF (hazard ratio [HR], 2.67; 95% confidence interval (CI), 2.43-2.94), 5.71-times higher risk for CAD (HR, 5.71; 95% CI, 5.14-6.33) and 2.94-times higher risk for ischemic stroke (HR, 2.94; 95% CI, 2.47-3.50). In the restricted cubic spline models, while a U-shaped trend was observed between HbA1c and the risk of AF, dose-dependent increases were observed between HbA1c and the risk of CAD and ischemic stroke regardless PRS tertile. CONCLUSIONS: Our results suggest that the nature of the dose-dependent relationship between HbA1c levels and cardiovascular disease in individuals with different PRS is outcome-specific. This adds to the evidence that PRS may play a role together with glycemic status in the development of cardiovascular disease.

Effect of Hind- and Fore-Foot Eversion on Positional and Rotational Displacement of the Knee in Standing Posture.

We investigated the effects of hindfoot and forefoot eversion on the knee's positional and rotational displacement, plantar pressure, and foot discomfort in a standing posture, beyond the traditional focus on external knee adduction moments (EKAM) in lateral wedge insoles. Twenty-six healthy participants underwent hindfoot eversion from 0 to 10 degrees in 2-degree increments, and forefoot eversion from 0 degrees to the hindfoot eversion angle in 2-degree increments in a standing posture. At each eversion angle, the knee's medial displacement, EKAM's moment arm decrease, plantar pressure changes, and foot discomfort were obtained and compared across varying angles. Both hindfoot-only and entire-foot eversion led to significant medial knee displacement and the EKAM's moment arm decrease, with more pronounced effects in entire-foot eversion. At each hindfoot eversion angle, increasing forefoot eversion resulted in significant medial knee displacement and EKAM's moment arm decrease. Lower leg rotations were not significantly affected in hindfoot-only eversion but displayed significant medial tilting and internal rotation in entire-foot eversion at specific combinations. Varying eversion angles significantly influenced the forefoot pressure, with heel pressure remaining unaffected. Notably, the lateral forefoot pressure increased significantly as the forefoot eversion angle increased, particularly at higher hindfoot eversion angles. Foot discomfort increased significantly with higher eversion angles, particularly in entire-foot eversion, and also increased significantly as the forefoot eversion angle increased at higher hindfoot eversion angles. Insole configurations incorporating 6-10 degrees of hindfoot eversion and 40-60% forefoot eversion of the hindfoot angle may offer optimized biomechanical support for knee osteoarthritis patients.

Predictors of in-hospital mortality after successful weaning of venoarterial extracorporeal membrane oxygenation in cardiogenic shock.

Limited knowledge exists regarding the predictors of mortality after successful weaning of venoarterial extracorporeal membrane oxygenation (ECMO). We aimed to identify predictors of in-hospital mortality in patients with cardiogenic shock (CS) after successful weaning from ECMO. Data were obtained from a multicenter registry of CS. Successful ECMO weaning was defined as survival with minimal mean arterial pressure (> 65 mmHg) for > 24 h after ECMO removal. The primary outcome was in-hospital mortality after successful ECMO weaning. Among 1247 patients with CS, 485 received ECMO, and 262 were successfully weaned from ECMO. In-hospital mortality occurred in 48 patients (18.3%). Survivors at discharge differed significantly from non-survivors in age, cardiovascular comorbidities, cause of CS, left ventricular ejection fraction, and use of adjunctive therapy. Five independent predictors for in-hospital mortality were identified: use of continuous renal replacement therapy (odds ratio 5.429, 95% confidence interval [CI] 2.468-11.940; p < 0.001), use of intra-aortic balloon pump (3.204, 1.105-9.287; p = 0.032), diabetes mellitus (3.152, 1.414-7.023; p = 0.005), age (1.050, 1.016-1.084; p = 0.003), and left ventricular ejection fraction after ECMO insertion (0.957, 0.927-0.987; p = 0.006). Even after successful weaning of ECMO, patients with irreversible risk factors should be recognized, and careful monitoring should be done for sign of deconditioning.

Clinical Practice Guideline for Stroke Rehabilitation in Korea-Part 1: Rehabilitation for Motor Function (2022).

This clinical practice guideline (CPG) is the fourth edition of the Korean guideline for stroke rehabilitation, which was last updated in 2016. The development approach has been changed from a consensus-based approach to an evidence-based approach using the Grading of Recommendations Assessment Development and Evaluation (GRADE) method. This change ensures that the guidelines are based on the latest and strongest evidence available. The aim is to provide the most accurate and effective guidance to stroke rehabilitation teams, and to improve the outcomes for stroke patients in Korea. Fifty-five specialists in stroke rehabilitation and one CPG development methodology expert participated in this development. The scope of the previous clinical guidelines was very extensive, making it difficult to revise at once. Therefore, it was decided that the scope of this revised CPG would be limited to Part 1: Rehabilitation for Motor Function. The key questions were selected by considering the preferences of the target population and referring to foreign guidelines for stroke rehabilitation, and the recommendations were completed through systematic literature review and the GRADE method. The draft recommendations, which were agreed upon through an official consensus process, were refined after evaluation by a public hearing and external expert evaluation.

Safety and therapeutic effects of personalized transcranial direct current stimulation based on electrical field simulation for prolonged disorders of consciousness: study protocol for a multi-center, double-blind, randomized controlled trial.

Background: Disorders of consciousness (DOC) resulting from acquired brain injury (ABI) increase the mortality rate of patients, complicate rehabilitation, and increase the physical and economic burden that DOC imposes on patients and their families. Thus, treatment to promote early awakening from DOC is vital. Transcranial direct current stimulation (tDCS) has shown great potential for promoting neuro-electrochemical activity. However, previous tDCS studies did not consider structural damage or head and brain lesions, so the applicability of the results to all DOC patients was limited. In this study, to establish a patient-specific tDCS treatment plan considering the brain lesions of and damage sustained by DOC patients, we considered the electric field calculated by a the "finite electric" three-dimensional brain model based on magnetic resonance images. This protocol was developed to aid tDCS treatment of actual patients, and to verify its safety and effectiveness. Methods/design: Twenty-four patients with DOC after ABI will be enrolled in this cross-over trial. All participants will receive typical rehabilitation combined with sham tDCS and typical rehabilitation plus personalized tDCS (P-tDCS). Each interventional period will last 2 weeks (30 min/day, 5 days/week). The primary outcome [score on the Korean version of the Coma Recovery Scale-Revised (K-CRS-R)] will be assessed at baseline and the end of the first day of the intervention. Secondary outcomes (K-CRS-R at 1 week and 2 weeks after experimental session and quantitative EEG changes quantitative electroencephalography changes) will be measured at baseline and the end of week 4. Adverse events will be recorded during each treatment session. Discussion: For patients with neurological disorders, tDCS has served as a painless, non-invasive, easily applied, and effective therapy for several decades, and there is some evidence that it can improve the level of consciousness of patients with DOC. However, variability in the effects on consciousness among subjects have been reported and personalized strategies are lacking. This protocol is for a randomized controlled trial designed to validate the effectiveness and safety of P-tDCS combined with typical rehabilitation for DOC. Clinical trial registration: https://cris.nih.go.kr, identifier KCT0007157.

Clinical Practice Guidelines for Oropharyngeal Dysphagia.

OBJECTIVE: Dysphagia is a common clinical condition characterized by difficulty in swallowing. It is sub-classified into oropharyngeal dysphagia, which refers to problems in the mouth and pharynx, and esophageal dysphagia, which refers to problems in the esophageal body and esophagogastric junction. Dysphagia can have a significant negative impact one's physical health and quality of life as its severity increases. Therefore, proper assessment and management of dysphagia are critical for improving swallowing function and preventing complications. Thus a guideline was developed to provide evidence-based recommendations for assessment and management in patients with dysphagia. METHODS: Nineteen key questions on dysphagia were developed. These questions dealt with various aspects of problems related to dysphagia, including assessment, management, and complications. A literature search for relevant articles was conducted using Pubmed, Embase, the Cochrane Library, and one domestic database of KoreaMed, until April 2021. The level of evidence and recommendation grade were established according to the Grading of Recommendation Assessment, Development and Evaluation methodology. RESULTS: Early screening and assessment of videofluoroscopic swallowing were recommended for assessing the presence of dysphagia. Therapeutic methods, such as tongue and pharyngeal muscle strengthening exercises and neuromuscular electrical stimulation with swallowing therapy, were effective in improving swallowing function and quality of life in patients with dysphagia. Nutritional intervention and an oral care program were also recommended. CONCLUSION: This guideline presents recommendations for the assessment and management of patients with oropharyngeal dysphagia, including rehabilitative strategies.

Structural Integrity of the Cerebellar Outflow Tract Predicts Long-Term Motor Function After Middle Cerebral Artery Ischemic Stroke.

BACKGROUND: The cerebellum plays a crucial role in functional movement by influencing sensorimotor coordination and learning. However, the effects of cortico-cerebellar connectivity on the recovery of upper extremity motor function after stroke have not been investigated. We hypothesized that the integrity of the cortico-cerebellar connections would be reduced in patients with a subacute middle cerebral artery (MCA) stroke, and that this reduction may help to predict chronic upper extremity motor function. METHODS: We retrospectively analyzed the diffusion-tensor imaging of 25 patients with a subacute MCA stroke (mean age: 62.2 ± 2.7 years; 14 females) and 25 age- and sex-matched healthy controls. We evaluated the microstructural integrity of the corticospinal tract (CST), dentatothalamocortical tract (DTCT), and corticopontocerebellar tract (CPCT). Furthermore, we created linear regression models to predict chronic upper extremity motor function based on the structural integrity of each tract. RESULTS: In stroke patients, the affected DTCT and CST showed significantly impaired structural integrity compared to unaffected tracts and the tracts in controls. When all models were compared, the model that used the fractional anisotropy (FA) asymmetry indices of CST and DTCT as independent variables best predicted chronic upper extremity motor function (R2 = .506, P = .001). The extent of structural integrity of the CPCT did not significantly differ between hemispheres or groups and was not predictive of motor function. CONCLUSIONS: We found evidence that microstructural integrity of the DTCT in the subacute phase of an MCA stroke helped to predict chronic upper extremity motor function, independent of CST status.

Post-Stroke Infections: Insights from Big Data Using Clinical Data Warehouse (CDW).

This study analyzed a digitized database of electronic medical records (EMRs) to identify risk factors for post-stroke infections. The sample included 41,236 patients hospitalized with a first stroke diagnosis (ICD-10 codes I60, I61, I63, and I64) between January 2011 and December 2020. Logistic regression analysis was performed to examine the effect of clinical variables on post-stroke infection. Multivariable analysis revealed that post-stroke infection was associated with the male sex (odds ratio [OR]: 1.79; 95% confidence interval [CI]: 1.49-2.15), brain surgery (OR: 7.89; 95% CI: 6.27-9.92), mechanical ventilation (OR: 18.26; 95% CI: 8.49-44.32), enteral tube feeding (OR: 3.65; 95% CI: 2.98-4.47), and functional activity level (modified Barthel index: OR: 0.98; 95% CI: 0.98-0.98). In addition, exposure to steroids (OR: 2.22; 95% CI: 1.60-3.06) and acid-suppressant drugs (OR: 1.44; 95% CI: 1.15-1.81) increased the risk of infection. On the basis of the findings from this multicenter study, it is crucial to carefully evaluate the balance between the potential benefits of acid-suppressant drugs or corticosteroids and the increased risk of infection in patients at high risk for post-stroke infection.

Early Invasive Strategy Based on the Time of Symptom Onset of Non-ST-Segment Elevation Myocardial Infarction.

BACKGROUND: A limitation of the current guidelines regarding the timing of invasive coronary angiography for patients with non-ST-segment elevation acute coronary syndrome is the randomization time. To date, no study has reported the clinical outcomes of invasive strategy timing on the basis of the time of symptom onset. OBJECTIVES: The aim of this study was to investigate the effect of invasive strategy timing from the time of symptom onset on the 3-year clinical outcomes of patients with non-ST-segment elevation myocardial infarction (NSTEMI). METHODS: Among 13,104 patients from the Korea Acute Myocardial Infarction Registry-National Institutes of Health, 5,856 patients with NSTE myocardial infarction were evaluated. The patients were categorized according to symptom-to-catheter (StC) time (<48 or ≥48 hours). The primary outcome was 3-year all-cause mortality. RESULTS: Overall, 3,919 patients (66.9%) were classified into the StC time <48 hours group. This group had lower all-cause mortality than the group with StC time ≥48 hours (7.3% vs 13.4%; P < 0.001). The lower risk for all-cause mortality in the group with StC time <48 hours group was consistent in all subgroups. Notably, emergency medical service use (HR: 0.31; 95% CI: 0.19-0.52) showed a lower risk for all-cause mortality than no emergency medical service use (HR: 0.54; 95% CI: 0.46-0.65; P value for interaction = 0.008). CONCLUSIONS: An early invasive strategy on the basis of StC time was associated with a decreased risk for all-cause mortality in patients with NSTEMI. Because the study was based on a prospective registry, the results should be considered hypothesis generating, highlighting the need for further research. (iCReaT Study No. C110016).

Fine-grained brain tissue segmentation for brain modeling of stroke patient.

Brain segmentation of stroke patients can facilitate brain modeling for electrical non-invasive brain stimulation, a therapy for stimulating brain function using an electric current. However, it remains challenging owing to its time-consuming, labor-dependent, and complicated pipeline. In addition, conventional tools that define lesions into one region rather than distinguishing between the stroke-affected regions and cerebrospinal fluid can lead to inaccurate treatment results. In this study, we first define a novel stroke-affected region as a detailed sub-region of the conventionally defined lesion. Subsequently, a novel comprehensive framework is proposed to segment head-brain and fine-level stroke-affected regions for normal controls and chronic stroke patients. The proposed framework consists of a time-efficient and precise deep learning-based segmentation model. The experiment results indicate that the proposed method perform better than the conventional deep learning-based segmentation model in terms of the evaluation metrics. The proposed method would be a valuable addition to brain modeling for non-invasive neuromodulation.

MRI-Based Personalized Transcranial Direct Current Stimulation to Enhance the Upper Limb Function in Patients with Stroke: Study Protocol for a Double-Blind Randomized Controlled Trial.

Transcranial direct current stimulation (tDCS) has been shown to have the potential to improve the motor recovery of the affected upper limbs in patients with stroke, and recently, several optimized tDCS methods have been proposed to magnify its effectiveness. This study aims to determine the effectiveness of personalized tDCS using brain MRI-based electrical field simulation and optimization, to enhance motor recovery of the upper limbs in the patients. This trial is a double-blind, randomized controlled trial in the subacute to chronic rehabilitation phase. Forty-two adult stroke patients with unilateral upper limb involvement will be randomly allocated to three groups: (1) personalized tDCS with MRI-based electrical field simulation and optimized stimulation, (2) conventional tDCS with bihemispheric stimulation of the primary motor cortex, and (3) sham tDCS. All three groups will undergo 10 intervention sessions with 30 min of 2-mA intensity stimulation, during a regular upper limb rehabilitation program over two weeks. The primary outcome measure for the motor recovery of the upper limb impairment is the Fugl-Meyer assessment for the upper extremity score at the end of the intervention, and the secondary measures include changes in the motor evoked potentials, the frequency power and coherence of the electroencephalography, performance in activities of daily living, and adverse events with a 1-month follow-up assessment. The primary outcome will be analyzed on the intention-to-treat principle. There is a paucity of studies regarding the effectiveness of personalized and optimized tDCS that considers individual brain lesions and electrical field characteristics in the real world. No feasibility or pivotal studies have been performed in stroke patients using brain MRI, to determine a lesion-specific tDCS simulation and optimization that considers obstacles in the segmentation and analysis of the affected brain tissue, such as ischemic and hemorrhagic lesions. This trial will contribute to addressing the effectiveness and safety of personalized tDCS, using brain MRI-based electrical field simulation and optimization, to enhance the motor recovery of the upper limbs in patients with stroke.